4. Regulatory Authority (RA)/ Competent Authority (CA)

4.1 Provide a list of documents needed to be submitted for RA/CA review and approval including the number of copies and/or translations as relevant.

The TGA administers two pathways for clinical trials, the Clinical Trials Notification (CTN) and Clinical Trials Approval (CTA) schemes. These provide an avenue through which 'unapproved' therapeutic goods may be lawfully supplied for use solely for experimental purposes in humans.

The choice of which route to use (CTN or CTA) lies firstly with the Australian clinical trial sponsor and then with the Human Research Ethics Committee (HREC) that approves the protocol.

The CTA route is generally designed for biologics and high-risk or novel treatments where there is no or limited knowledge of safety. For medical device trials, the CTA scheme may be more appropriate where the experimental device introduces new technology, new material, or a new treatment concept that has not been evaluated previously in clinical trials in any country. The CTA scheme should also be considered for medical devices that pose a risk of serious patient harm.

The determining factor for an HREC is whether the committee has access to appropriate scientific and technical expertise in order to assess the safety of the product.

Under the Australian regulatory framework for biologicals, certain Class 4 biologicals are not able to be supplied under the CTN Scheme and must be submitted under the CTA scheme. If a Sponsor is unclear of which pathway to follow, they should consult with TGA.

CTA Application

The CTA Scheme is an approval process involving the following:

• A sponsor submits an application to TGA seeking approval to supply 'unapproved' therapeutic goods in a clinical trial. The application must be accompanied by the relevant fee.
• TGA evaluates summary information about the product including relevant, but limited, scientific data (which may be preclinical and early clinical data) prior to the start of a trial.
• The HREC is responsible for considering the scientific and ethical issues of the proposed trial protocol.
• The sponsor must notify TGA of each trial conducted using the unapproved therapeutic good(s) approved in the CTA application.

Part 1: The application

Part 1 is the formal CTA application. It must be completed by the sponsor of the trial and submitted to TGA with data for evaluation. The appropriate fee must be paid.

The CTA application form can be emailed to TGA. Supporting data for the CTA application should be provided in electronic format. 

Supply of unapproved therapeutic goods under the clinical trial approval (CTA) scheme - Part 1 The CTA application (docx,134kb)

Part 2: Notification of the conduct of a trial under the CTA scheme

Part 2 is used to notify us of the commencement of each new trial conducted as per the usage guidelines approved in the CTA application. There is no fee for notification of trials under the CTA scheme.

Supply of unapproved therapeutic goods under the clinical trial approval (CTA) scheme - Part 2 Notification of the conduct of a trial under the CTA scheme (docx,135kb)

The evaluation of a CTA application includes consideration of the manufacturing and quality and safety data in conjunction with the trial's usage guidelines, to inform a risk-benefit decision by TGA on whether or not to approve the clinical trial. Any significant changes to the information provided in support of the trial are considered a ‘variation’ and need to be approved as they have the potential to affect the initial decision to approve a trial.

CTN Application

The CTN Scheme is a notification process involving the following:

• The Australian clinical trial sponsor must notify TGA of the intent to sponsor a clinical trial involving an 'unapproved' therapeutic good. This must take place before starting to use the goods. The notification form must be submitted online and accompanied by the relevant fee.
• TGA may give the sponsor of the trial written notice to provide specified information relating to goods notified in the CTN form.
• TGA does not evaluate any data relating to the clinical trial at the time of submission. The Human Research Ethics Committee (HREC) reviews the scientific validity of the trial design, the balance of risk versus harm of the therapeutic good, and the ethical acceptability of the trial process, and approves the trial protocol. The HREC is also responsible for monitoring the conduct of the trial.
• The institution or organization at which the trial will be conducted, referred to as the 'Approving Authority', gives the final approval for the conduct of the trial at the site, having due regard to advice from the HREC.
• It is the responsibility of the sponsor to ensure that all relevant approvals are in place before supplying the 'unapproved' therapeutic goods in the clinical trial.

The online CTN form can be accessed via the TGA business services website- external site. Sponsors are required to hold a TGA business services account in order to make such an application.

4.2 Time required for RA/CA review and approval process and turnaround time if any query is raised during the review process.

CTA

There is no formally legislated review timeline for a CTA application; it depends on the complexity of the product. The review timeline is typically 2 – 3 months depending on how many questions are raised by TGA and how quickly a Sponsor is able to respond.

CTN

There is no formal approval of a CTN. Once the trial is listed on the TGA trial database, the Sponsor may proceed. This typically takes 7 – 14 days from the time of application of the CTN.

4.3 Does the regulation support electronic submission?

Yes. All documentation should be submitted electronically.

4.4 Does the regulation require the applicant to be a Principal Investigator (PI)/Chief Investigator (CI)? Are there any exceptions allowed?

No. The applicant is typically the Sponsor (the pharma company, or their CRO). There may be exceptions to this as long as the sponsor is an Australian legal entity. 

4.5 Please describe the process of RA/CA submission for clinical trial approval.

Please refer to Section 4.1 above.

4.6 Does the RA/CA provide written acknowledgment of the submitted application? If not, describe how the application is tracked.

Yes. TGA provides an acknowledgment of the application upon receipt.

4.7 What is the relevant RA/CA fee in local currency/USD? Please provide as much information as possible (e.g. if the fee is different for notification/approval, initial submission, amendment, study with IMPD and study without IMPD, etc.)

The sponsor is responsible for paying a fee to the Therapeutic Goods Administration (TGA) to submit an application under the clinical trial notification (CTN) or clinical trial approval (CTA) (formerly known as clinical trial exemption (CTX)) scheme for evaluation. The fees effective July 2023 are as follows:

• $410 Australian dollars for unapproved medicines CTN, and for each notification of one (1) or more additional trial sites
• $1,954 Australia dollars for unapproved medicines CTA (30-day evaluation)
• $537 Australian dollars for unapproved medicines CTA - variation (30-day evaluation)
• $24,285 Australian dollars for unapproved medicines CTA (50-day evaluation)
• $6,628 Australian dollars for unapproved medicines CTA – variation (50-day evaluation)
• $410 Australian dollars for unapproved biologicals CTN, and for each notification of one (1) or more additional trial sites
• $29,574 Australian dollars for unapproved biologicals CTA
• $8,069 Australian dollars for unapproved biologicals CTA – variation

https://www.tga.gov.au/sites/default/files/2023-06/Fees-and-charges-summary-1-July-2023.pdf

4.8 Does RA/CA accept checks or can payment be made electronically? Please provide details on (1) A/C number; (2) A/C Name; (3) Sort Code; (4) Swift Code; (5) Bank address, etc. Where can remittance advice notices be sent?

Regulatory fees and charges may be paid online, by cheque, or by direct deposit. Online payment by credit card is the preferred payment option, and all payments must be in Australian dollars.

Online payment is made via the TGA Online Payment Portal. Once the payment has been finalized, the Portal will confirm that payment has been successful, and the user may request an email confirmation.

4.9 Is there any guidance tool available for making an electronic application? If yes, provide the link and/or step-by-step instructions.

Instructions on completion of the CTN electronic form are provided in the CTN User Manual.

4.10 Does RA/CA require any screenshots/mock screens for participant-facing materials?

No.